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Volume 14
Issue 11
10.3390/jcm14113751
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Systematic Review

An Integrative Review of Potential Diagnostic Biomarkers for Complex Regional Pain Syndrome

by
Revelino Lopes
1,2,*,
André Santos
2,
Teresa Gomes
2,
Júlia Ribeiro
2,
Ivone Rodrigues
2,
Bruno Paiva
2,
Isa Nzwalo
1,
Deise Catamo
1,
Jamal Baco
1,
Helena Buque
1,
Marta Botelho
1,3,4,
Sandra Pais
5 and
Hipólito Nzwalo
1,3,4,*
1
Faculty of Medicine and Biomedical Sciences, University of Algarve, 8005-139 Faro, Portugal
2
Faro Unit Hospital, Local Health Unit of Algarve, 8000-386 Faro, Portugal
3
Aging and Cerebrovascular Research Group, Algarve Biomedical Research Institute, 8005-139 Faro, Portugal
4
Algarve Biomedical Center, 8005-139 Faro, Portugal
5
Comprehensive Health Research Centre-CHRC, University of Évora, 7004-516 Évora, Portugal
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(11), 3751; https://doi.org/10.3390/jcm14113751
Submission received: 25 April 2025 / Revised: 22 May 2025 / Accepted: 25 May 2025 / Published: 27 May 2025
(This article belongs to the Section Immunology)
Versions Notes

Abstract

Background: Complex regional pain syndrome (CRPS) is a rare, chronic, painful, neurological, debilitating disorder. Despite the substantial impact on quality of life, diagnosis remains challenging due to its complex pathophysiology and subjective clinical criteria. This integrative review aims to synthesize current research on potential diagnostic biomarkers for CRPS. Methods: A systematic search was conducted using the PubMed and Scopus databases to identify relevant studies published until January 2025. Inclusion criteria focused on adult CRPS patients, with studies examining diagnostic or predictive biomarkers. Results: Key findings highlight the role of inflammatory and immune-related biomarkers, such as elevated levels of cytokines (IL-6, TNF-α), immune cell infiltration, and specific autoantibodies. Neuropeptides, including substance P and calcitonin gene-related peptide, were associated with pain sensitization in acute phases, though their levels normalized in chronic stages. Additionally, genetic and epigenetic markers, brain imaging, and neurophysiological alterations provided insights into CRPS pathogenesis, emphasizing the dynamic nature of these biomarkers across disease stages. Conclusions: This review underscores the need for further research to integrate these biomarkers into diagnostic frameworks, which could enhance early diagnosis and treatment strategies for CRPS.
Keywords: complex regional pain syndrome; biomarkers; cytokines; neuropeptides; inflammation; immune response complex regional pain syndrome; biomarkers; cytokines; neuropeptides; inflammation; immune response

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MDPI and ACS Style

Lopes, R.; Santos, A.; Gomes, T.; Ribeiro, J.; Rodrigues, I.; Paiva, B.; Nzwalo, I.; Catamo, D.; Baco, J.; Buque, H.; et al. An Integrative Review of Potential Diagnostic Biomarkers for Complex Regional Pain Syndrome. J. Clin. Med. 2025, 14, 3751. https://doi.org/10.3390/jcm14113751

AMA Style

Lopes R, Santos A, Gomes T, Ribeiro J, Rodrigues I, Paiva B, Nzwalo I, Catamo D, Baco J, Buque H, et al. An Integrative Review of Potential Diagnostic Biomarkers for Complex Regional Pain Syndrome. Journal of Clinical Medicine. 2025; 14(11):3751. https://doi.org/10.3390/jcm14113751

Chicago/Turabian Style

Lopes, Revelino, André Santos, Teresa Gomes, Júlia Ribeiro, Ivone Rodrigues, Bruno Paiva, Isa Nzwalo, Deise Catamo, Jamal Baco, Helena Buque, and et al. 2025. "An Integrative Review of Potential Diagnostic Biomarkers for Complex Regional Pain Syndrome" Journal of Clinical Medicine 14, no. 11: 3751. https://doi.org/10.3390/jcm14113751

APA Style

Lopes, R., Santos, A., Gomes, T., Ribeiro, J., Rodrigues, I., Paiva, B., Nzwalo, I., Catamo, D., Baco, J., Buque, H., Botelho, M., Pais, S., & Nzwalo, H. (2025). An Integrative Review of Potential Diagnostic Biomarkers for Complex Regional Pain Syndrome. Journal of Clinical Medicine, 14(11), 3751. https://doi.org/10.3390/jcm14113751

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